Incorporation of cholyl-nitroso-cysteine bile salts in Pluronic hydrogels: impact on the micellar packing

Abstract

Micellar hydrogels composed of block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), denoted Pluronics, have been used for an ample range of applications, including biomaterials, cosmetics, and drug delivery. Bile salts, which are amphiphilic molecules, have shown synergy self-assembly effect with Pluronics, affecting the micellar properties, and enhancing drug encapsulation efficiency and absorption. Our group has been using Pluronic hydrogels as a matrix to release nitric oxide (NO) locally from primary S-nitrosothiols (RSNOs) in biomedical applications. In these systems, the NO release profiles are governed by the dimerization reaction of the RSNOs located in the hydrophilic PEO corona of the micelles and in the intermicellar space. The incorporation of RSNOs conjugated to bile salts (bile salt-SNO) into Pluronic hydrogels should anchor the hydrophobic part of these molecules to the PPO hydrophobic core of the micelles. This innovative approach is expected to lead to more stable Pluronic/RSNOs systems, in which NO release can be controlled photochemically. Investigating the localization of bile salt-SNO in the Pluronic micellar nanostructure is fundamental to understand and modulate the NO release from these hydrogels. In this study, we will use micro-differential scanning calorimetry, dynamic light scattering, and small angle X-ray scattering to characterize bile salt-SNO-containing Pluronic hydrogels and to correlate their nanostructure with their NO release profiles. The development of bile salt-SNO conjugates may lead to novel amphiphilic NO-releasing compounds and their incorporation into micellar Pluronic hydrogels may further expand the repertoire of local NO release, opening the way new medical applications.